甘氨双唑钠提高肝动脉阻断结合外放射治疗大鼠肝移植瘤的疗效

Metronidazol amino acid augments effects of hepatic arterial occlusion combined with radiotherapy in a rat liver tumor model

目的:观察乏氧放射增敏剂甘氨双唑钠(CM)的应用能否提高肝动脉栓塞(TAE)结合外放射治疗肝肿瘤的效果。方法: 采用大鼠肝内移植Walker256 肿瘤模型,以肝动脉结扎(HAL)的方法阻断肝动脉血供,模拟TAE 治疗。荷瘤大鼠分为对照组、HAL组、HAL+外放射(RT)组、HAL+RT+CM组。观察治疗后肝内肿瘤的大小变化,冷冻切片观察肝肿瘤的坏死情况,原位杂交法检测肿瘤组织VEGF mRNA表达水平,石蜡切片观察肺转移灶情况。结果:与对照组相比,HAL+RT组、HAL+ RT+ CM组的肿瘤体积明显缩小,P<0 .01, HAL+RT+CM组肿瘤体积较HAL+RT组进一步缩小,但差异无统计学意义,P> 0. 05。与对照组相比,仅HAL+RT+CM组肿瘤坏死程度明显加重,P<0 05。与对照组相比,HAL组VEGF mRNA表达水平无明显改变,而HAL+RT、HAL+RT+CM组表达水平明显下降,P<0 .05。各组间肺转移率差异无统计学意义,P<0 .05。结论:在肝动脉阻断结合外放射综合治疗中加入CM促进肿瘤的坏死,并有进一步缩小肿瘤体积的趋势;对VEGFmRNA表达与肺转移率无明显影响。

OBJECTIVE: To explore if a new radiosensitizer metronidazol amino acid (CM) can augment the effects of hepatic arterial embolization combined with radiotherapy for transplanted cancer in rat liver. METHODS:Walker 256 carcinosarcoma was transplanted into rat liver to establish a liver cancer model. Hepatic arterial ligation (HAL) was used to block the hepatic arterial blood supply, and to simulate hepatic arterial embolization. Rats bearing tumor were divided into four groups: control group, HAL group, HAL combined with radiotherapy (HAL+RT) group, and HAL+RT plus CM ( HAL+RT+CM) group. Changs in tumor volume and tumor growth inhibiting rate after therapy were evaluated, and frozen sections were used to observe the degree of necrosis in tumor. The expression of VEGF mRNA was detected by in situ hybridization. Lung metastasis was observed by paraffin sections. RESULTS:The tumor volumes in HAL+RT group and HAL+RT+CM group were smaller than the volume in the control group,P<0.01. Compared with HAL+RT group, the tumor volume in HAL+RT+CM group decreased further but not significantly,P>0.05. Compared with the control group, the degree of tumor necrosis increased only in HAL+RT+CM group,P<0.05. The expression of VEGF mRNA decreased significantly in HAL+RT group and HAL+RT+CM group compared with the control group,P<0.05. There was no significant difference in metastasis rate among the four groups,P>0.05. CONCLUSIONS:Introducing CM into the combined therapy with hepatic arterial occlusion and radiotherapy for transplanted cancer in rat′s liver can promote tumor necrosis, and has the trend in reducing tumor volume.However,it has no significant influence on the expression of VEGF and lung metastasis rate.